The key questions to be addressed are as follows: (1) Project 1 - what is the role of the natural immune response to HTLV-III in individuals infected with the virus? (2) Project 2 - which are the epitopes on the virus envelope glycoproteins that can be exploited for vaccine production? (3) Project 3 - what is the effect of HTLV-III and its components on cellular immune function? (4) Project 4 - what is the significance of macrophage dysfunction in AIDS and is this mediated by HTLV-III or its gene products? (5) Project 5 - what are the consequences of HTLV-III infection in hemophiliacs and how does this differ from other risk groups and (6) Project 6 - can one develop effective anti-viral agents for interventive approaches in already infected individuals? The approaches to be used to answer these questions will employ specialized biological assay systems, native and recombinant viral gene products, synthetic peptides, monoclonal antibodies, anti-viral compound, and mutant virus strains. In addition to pre-clinical studies in vitro or in animal models, actual clinical trials with promising vaccines and anti-viral agents will be engaged.